BACKGROUND AND AIMS

The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques.

METHODS

Carotid plaques ( = 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of , , , and was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection.

RESULTS

At mRNA level, and were significantly higher expressed in stable carotid plaques compared with controls ( = 0.011,  < 0.001 and  < 0.001). mRNA expression was successively augmented toward unstable plaques ( < 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable ( = 0.001,  < 0.001 and  = 0.035, respectively) and unstable ( = 0.003,  < 0.001 and  = 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed expression as well. For , only microdissected areas with macrophages were positive.

CONCLUSION

Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.